NM_172217.5:c.*3249T>C

Variant names:

• chr15-81312047-T-C
• rs4778641
• NM_172217.5:c.*3249T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172217.5(IL16):​c.*3249T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,672 control chromosomes in the GnomAD database, including 17,055 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (17055 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: IL16 NM_172217.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 14 publications found

Genes affected

IL16 (HGNC:5980): (interleukin 16) The protein encoded by this gene is a pleiotropic cytokine that functions as a chemoattractant, a modulator of T cell activation, and an inhibitor of HIV replication. The signaling process of this cytokine is mediated by CD4. The product of this gene undergoes proteolytic processing, which is found to yield two functional proteins. The cytokine function is exclusively attributed to the secreted C-terminal peptide, while the N-terminal product may play a role in cell cycle control. Caspase 3 is reported to be involved in the proteolytic processing of this protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

STARD5 (HGNC:18065): (StAR related lipid transfer domain containing 5) Proteins containing a steroidogenic acute regulatory-related lipid transfer (START) domain are often involved in the trafficking of lipids and cholesterol between diverse intracellular membranes. This gene is a member of the StarD subfamily that encodes START-related lipid transfer proteins. The protein encoded by this gene is a cholesterol transporter and is also able to bind and transport other sterol-derived molecules related to the cholesterol/bile acid biosynthetic pathways such as 25-hydroxycholesterol. Its expression is upregulated during endoplasmic reticulum (ER) stress. The protein is thought to act as a cytosolic sterol transporter that moves cholesterol between intracellular membranes such as from the cytoplasm to the ER and from the ER to the Golgi apparatus. Alternative splicing of this gene produces multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL16	NM_172217.5	c.*3249T>C		3_prime_UTR_variant	Exon 19 of 19	ENST00000683961.1	NP_757366.2
STARD5	NM_181900.3	c.*1209A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000302824.7	NP_871629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL16	ENST00000683961.1	c.*3249T>C		3_prime_UTR_variant	Exon 19 of 19		NM_172217.5	ENSP00000508085.1
STARD5	ENST00000302824.7	c.*1209A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_181900.3	ENSP00000304032.6

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69297 AN: 151546 Hom.: 17013 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.459

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.458 AC: 69392 AN: 151668 Hom.: 17055 Cov.: 32 AF XY: 0.449 AC XY: 33282 AN XY: 74106

African (AFR) AF: 0.658 AC: 27166 AN: 41296

American (AMR) AF: 0.379 AC: 5773 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1574 AN: 3466

East Asian (EAS) AF: 0.498 AC: 2558 AN: 5140

South Asian (SAS) AF: 0.291 AC: 1398 AN: 4812

European-Finnish (FIN) AF: 0.339 AC: 3564 AN: 10526

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.381 AC: 25850 AN: 67874

Other (OTH) AF: 0.464 AC: 975 AN: 2102

Alfa AF: 0.411 Hom.: 25146

Bravo AF: 0.474

Asia WGS AF: 0.419 AC: 1457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.37
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4778641; hg19: chr15-81604388;